| 1. |
- Bhattachariya, Anirban, et al.
(författare)
-
PYK2 selectively mediates signals for growth versus differentiation in response to stretch of spontaneously active vascular smooth muscle.
- 2014
-
Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 2:7
-
Tidskriftsartikel (refereegranskat)abstract
- Stretch of vascular smooth muscle stimulates growth and proliferation as well as contraction and expression of contractile/cytoskeletal proteins, all of which are also regulated by calcium-dependent signals. We studied the role of the calcium- and integrin-activated proline-rich tyrosine kinase 2 (PYK2) in stretch-induced responses of the rat portal vein loaded by a hanging weight ex vivo. PYK2 phosphorylation at Tyr-402 was increased both by a 10-min stretch and by organ culture with load over several days. Protein and DNA synthesis were reduced by the novel PYK2 inhibitor PF-4594755 (0.5-1 μmol/L), while still sensitive to stretch. In 3-day organ culture, PF-4594755 caused maintained myogenic spontaneous activity but did not affect contraction in response to high-K(+) (60 mmol/L) or to α1-adrenergic stimulation by cirazoline. Basal and stretch-induced PYK2 phosphorylation in culture were inhibited by PF-4594755, closely mimicking inhibition of non-voltage-dependent calcium influx by 2-APB (30 μmol/L). In contrast, the L-type calcium channel blocker, nifedipine (1 μmol/L) eliminated stretch-induced but not basal PYK2 phosphorylation. Stretch-induced Akt and ERK1/2 phosphorylation was eliminated by PF-4594755. PYK2 inhibition had no effect on mRNA expression of several smooth muscle markers, and stretch-sensitive SM22α synthesis was preserved. Culture of portal vein with the Ang II inhibitor losartan (1 μmol/L) eliminated stretch sensitivity of PYK2 and Akt phosphorylation, but did not affect mRNA expression of smooth muscle markers. The results suggest that PYK2 signaling functionally distinguishes effects of voltage- and non-voltage-dependent calcium influx. A small-molecule inhibitor of PYK2 reduces growth and DNA synthesis but does not affect contractile differentiation of vascular smooth muscle.
|
|
| 2. |
- Holm, Anders, et al.
(författare)
-
Down-regulation of endothelial cell estrogen receptor expression by the inflammation promoter LPS.
- 2010
-
Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 319, s. 8-13
-
Tidskriftsartikel (refereegranskat)abstract
- Endothelial cells express both estrogen receptor (ER) alpha and beta. The objective of this study was to investigate if and how mediators of inflammation regulate endothelial cell ERalpha and ERbeta expression. ERalpha and ERbeta transcript and protein expression were determined by real-time quantitative PCR and Western blotting, respectively, in endothelial cell line bEnd.3 cells stimulated with the inflammation promoter lipopolysaccharide (E. coli LPS). Stimulation with LPS (500ng/ml and 10mug/ml) for 4 days reduced both ERalpha and ERbeta mRNA levels. The glucocorticoid dexamethasone (1muM) had no effect on LPS-induced attenuation of ERalpha and beta transcript expression. Full-length 66-67kDa ERalpha protein was unaffected by 4 days stimulation with LPS, while the 46-kDa ERalpha isoform was reduced by about 20%. ERbeta protein was reduced by about 40% by LPS at 4 days. Treatment with 17beta-estradiol (E(2), 100nM) for 4 days increased ERbeta mRNA by about 8 times but had no effect on ERalpha mRNA level. The E(2)-induced increase in ERbeta transcript was not associated with increased ERbeta protein. E(2) increased ERbeta mRNA expression also in the presence of LPS, suggesting that inflammation-induced impairment of ERbeta signalling is rescued by estrogen.
|
|
| 3. |
- Myhrene Steffenak, Anne Kjersti, 1955-
(författare)
-
Mental Distress and Psychotropic Drug Use among Young People, and Public Health Nurses` Conceptions of Their Roles
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aim: The overall aim of this thesis was to study mental distress, health and lifestyle habits, social factors and psychotropic drug use by young people, and how PHNs conceive their roles in relation to this.Methods: Quantitative and qualitative methods were used. Study I included data from the Norwegian Youth Health Study (NYHS, 11 620 participants, aged 15-16 years) (2000–2003) linked to the Norwegian Prescription Database (NorPD) (2004–2009). Study II included prescription data on psychotropic drugs among 15-16 year olds from the NorPD (2006–2010). Eight young people were interviewed and qualitative content analysis was used to analyse the data (III). Study IV included interviews with 20 Public Health Nurses (PHN), and was analysed using a phenomenographic approach.Main results: Mental distress was reported among 15.5% of the adolescents non-users of psychotropic drugs, 75% of whom were girls. In both genders reporting mental distress, incident psychotropic use was higher one to nine years, up to 27.7% among girls, as compared with the rest of the participants. In addition, health, lifestyle habits and social factors were associated with incident use (I). Psychotropic drug use increased during 2006–2010, hypnotics and melatonin accounted for most of the increase. In total, 16.4% of all incident psychotropic drug users in 2007 were still having prescriptions dispensed in 2010 (II). Young people experience both beneficial and undesired effects from psychotropic drugs. Access to professional support and follow-up was experienced as insufficient. Life with family, friends, school and work was influenced by psychotropic drug use, and they were afraid of being lonely and stigmatized (III). The PHNs conceived their roles in relation to young people as; the discovering PHNs who became aware of psychotropic drug use in the health dialogues and chose either to act or not to act in relation to this. Those PHNs who took action continued to be the cooperating PHNs who cooperated with the young people, their families, schools, and others. If cooperation was established, the supporting PHNs teach and support the young people in relation to psychotropic drug use (IV).Conclusions: Attention must be paid to poor mental health and increasing psychotropic drug use by young people. Advances in knowledge, treatment and follow-up are needed. The prevalence of mental distress among young people, with differences between the genders, as well as between socioeconomic groups, should have consequences for health promotion strategies. PHNs in Norway, working in health centres and schools, have responsibility and opportunity to identify and follow-up young people with mental health problems.
|
|
